{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T01:11:23Z","timestamp":1745284283829,"version":"3.37.3"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,11,17]],"date-time":"2014-11-17T00:00:00Z","timestamp":1416182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007479","name":"Fondazione CARIPARO","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007479","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Stevanato Group SPA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Severe copper deficiency leads in humans to a treatable multisystem disease characterized by anaemia and degeneration of spinal cord and nerves, but its mechanisms have not been investigated. We tested whether copper deficit leads to alterations in fundamental copper\u2010dependent proteins and in iron metabolism in blood and muscles of patients affected by copper deficiency myeloneuropathy, and if these metabolic abnormalities are associated with compensatory mechanisms for copper maintenance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated the expression of critical copper enzymes, of iron\u2010related proteins, and copper chaperones and transporters in blood and muscles from five copper\u2010deficient patients presenting with subacute sensory ataxia, muscle paralysis, liver steatosis and variable anaemia. Severe copper deficiency was caused by chronic zinc intoxication in all of the patients, with an additional history of gastrectomy in two cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The antioxidant enzyme <jats:styled-content style=\"fixed-case\">SOD<\/jats:styled-content>1 and subunit 2 of cytochrome c oxidase were significantly decreased in blood cells and in muscles of copper\u2010deficient patients compared with controls. In muscle, the iron storage protein ferritin was dramatically reduced despite normal serum ferritin, and the expression of the haem\u2010proteins cytochrome c and myoglobin was impaired. Muscle expression of the copper transporter <jats:styled-content style=\"fixed-case\">CTR<\/jats:styled-content>1 and of the copper chaperone <jats:styled-content style=\"fixed-case\">CCS<\/jats:styled-content>, was strikingly increased, while antioxidant protein 1 was diminished.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>copper\u2010dependent enzymes with critical functions in antioxidant defences, in mitochondrial energy production, and in iron metabolism are affected in blood and muscles of patients with profound copper deficiency leading to myeloneuropathy. Homeostatic mechanisms are strongly activated to increase intracellular copper retention.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12111","type":"journal-article","created":{"date-parts":[[2013,12,23]],"date-time":"2013-12-23T13:56:16Z","timestamp":1387806976000},"page":"888-898","source":"Crossref","is-referenced-by-count":13,"title":["Impaired copper and iron metabolism in blood cells and muscles of patients affected by copper deficiency myeloneuropathy"],"prefix":"10.1111","volume":"40","author":[{"given":"Marco","family":"Spinazzi","sequence":"first","affiliation":[{"name":"Neuromuscular Laboratory Department of Neurosciences University of Padova  Padova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Sghirlanzoni","sequence":"additional","affiliation":[{"name":"Istituto C. 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